| Eligibility |
Inclusion Criteria:
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol
- Have a histologically confirmed or cytologically confirmed diagnosis of stage IIIB or
stage IV NSCLC
- Have a performance status of 2 on the Eastern Cooperative Oncology Group (ECOG)
performance status with any age, or age >= 70 with ECOG PS of 0, 1, or 2, on the day
of signing informed consent
- Patients must have measurable disease based on Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 as determined by local site investigator/radiology assessment.
Target lesions situated in previously irradiated area are considered measurable if
progression has been demonstrated in such lesions
- Have not received prior systemic treatment for their advanced/metastatic NSCLC.
Subjects who received adjuvant or neoadjuvant therapy are eligible if the
adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development
of metastatic disease
- Body weight > 30 kg
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.5 (>= 1500 per mm^3)
- Platelet count >= 100) x 10^9/L (>= 100,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). (This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed if =< 3.0 x institutional upper limit of
normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal unless liver metastases are present, in
which case it must be =< 5 x ULN
- Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL > 40 mL/min
by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
- The effects of the study drug on the developing human fetus are unknown. For this
reason female of child-bearing potential (FCBP) must have a negative serum or urine
pregnancy test prior to starting therapy
- FCBP and men must agree to use adequate contraception (at least one highly effective
method and one additional method of birth control at the same time or complete
abstinence) prior to study entry, for the duration of study participation and for at
least 4 months following study drug discontinuation. Should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately. A female of childbearing potential
(FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12
consecutive months (if age > 55 years); if the female subject is < 55 years and she
has been naturally postmenopausal for > 1 year her reproductive status has to be
verified by additional lab tests (< 20 estradiol OR estradiol < 40 with follicle
stimulating hormone [FSH] > 40 in women not on estrogen replacement therapy)
- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
Exclusion Criteria:
- Participation in another clinical study with an investigational product during the
last 4 weeks
- ECOG PS 3 or higher
- Prior systemic therapy for the treatment of advanced or metastatic NSCLC
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
- Completed palliative radiotherapy within 7 days of the first dose of trial treatment
- Has a known sensitivity to any component of carboplatin, pemetrexed, paclitaxel, or
durvalumab
- Is unable to unwilling to take folic acid of vitamin b12 supplementation (if
non-squamous histology)
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the
exception of vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after
consultation with the study physician
- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the study
physician
- Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable
- History of allogenic organ transplantation
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion:
- Patients with vitiligo
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially increase
risk of incurring adverse events (AEs) or compromise the ability of the patient to
give written informed consent
- Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate
risk prostate cancer, or in situ carcinoma fully resected) unless disease free for a
minimum of one year
- History of leptomeningeal carcinomatosis
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are clinically stable for at least 2 weeks. Subjects with asymptomatic brain
metastases may participate, but will require regular imaging of the brain as a site of
disease
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Patients positive for 20. Active infection including tuberculosis (clinical
evaluation that includes clinical history, physical examination and radiographic
findings, and TB testing in line with local practice), hepatitis B (known positive HBV
surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are
eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed << 10 mg/day >> of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., computed
tomography [CT] scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
30 days after the last dose of IP
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients
- Patients may not have received prior anti-PD-1, anti PD-L1 including durvalumab or
anti CTLA-4 drugs
- Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements
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